Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice

Ryeonghwa Kang, Kyungdeok Kim, Yewon Jung, Sang Han Choi, Chanhee Lee, Geun Ho Im, Miram Shin, Kwangmin Ryu, Subin Choi, Esther Yang, Wangyong Shin, Seungjoon Lee, Suho Lee, Zachary Papadopoulos, Ji Hoon Ahn, Gou Young Koh, Jonathan Kipnis, Hyojin Kang, Hyun Kim, Won Ki ChoSoochul Park, Seong Gi Kim, Eunjoon Kim

Research output: Contribution to journalArticlepeer-review


AU Autism: Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly spectrum disorders (ASD) frequently accompany macrocephaly, : which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.

Original languageEnglish
Article numbere3002596
JournalPLoS biology
Issue number5 May
Publication statusPublished - 2024 May

Bibliographical note

Publisher Copyright:
Copyright: © 2024 Kang et al.

ASJC Scopus subject areas

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences


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